抗心律失常新药关附甲素血浓度测定的方法学研究

抗心律失常新药关附甲素血浓度测定的方法学研究

杨丽莉, 杨巷菁, 刘静涵, 李耐三, 邱宁婴

1. 南京金陵医院, 南京 210002;
2. 中国药科大学, 南京 210009

收稿日期:1991-09-24 修回日期:1992-02-10 出版日期:1992-06-15 发布日期:1992-06-15

Studies on the Analytical Method for a New Antiarrhythmic Guanfu Base A in Rabbit Plasma

Li-Li Yang, Xiang-Jing Yang, Jing-Han Liu, Nai-San Li, Ning-Ying Qiu

1. Department of Instrument Analysis, Jinling Hospital, Nanjing 210002;
2. China Pharmaceutical University, Nanjing 210009

Received:1991-09-24 Revised:1992-02-10 Online:1992-06-15 Published:1992-06-15

摘要/Abstract

摘要： 抗心律失常新药关附甲素 (Guan-fu base A, GFA) 为一种C20-二萜类生物碱, 1966年由我国首次从黄花乌头(Aconitum coreanum(Levl.) Raipaics) 的块根中分离得到。GFA与三氟醋酐(TFAA)反应, 迅速定量地生成关附甲素双-三氟乙酸酯 (GFA-TFAA), 其结构经GC-MSD 分析得到证实。GC-ECD 法对GFA 的检测线性范围宽(10~20000 ng/ml, r = 0.9984), 血浆中平均回收率为97.52%。日间及日内差的变异系数分别为9%及7%以下。该法用于GFA 的临床前药理研究。GFA 三种剂量静脉给药6小时内的家兔血药浓度范围是: 0.338±0.014至13.459±5.392 μg/ml (10 mg/kg), 0.133±0.038至2.546±0.480 μg/ml (2 mg/kg)以及45.25±10.34至535.86±24.36 ng/ml (0.4 mg/kg)。

关键词: 关附甲素, 气相色谱-电子捕获检测, 三氟醋酐, 衍生化反应, 血浆浓度

Abstract: Guan-fu base A(GFA), a new antiarrhythmic alkaloid with a structure of C20-diterpenoid could react rapidly and quantitatively with trifluoroacetic anhydride (TFAA) to produce GFA-TFAA of which the structure was identified by GC-MSD. There was a wide linear range of the GC-ECD method from 10 to 20000 ng/ml (r = 0.9984). The average recovery of GFA from the spiked plasma was 97.52%. The coefficients of variation of within-day and between-day were less than 7% and 9%, respectively. The method was used in the preclinical experiment of pharmacology of GFA and the results showed that GFA concentrations in rabbits' plasma within 6 hours after the administration ranged from 0.338±0.014 to 13.459±5.393 μg/ml for dosage 10mg/kg, from 0.133±0.038 to 2.546±0.480 μg/ml for dosage 2 mg/kg and from 45.25±10.34 to 535.86±24.36 ng/ml for dosage 0.4 mg/kg.

Key words: Guan-fu base A (GFA), GC-ECD, Trifluoroacetic anhydride (TFAA), Derivatization, Plasma concentration

Supporting:

杨丽莉, 杨巷菁, 刘静涵, 李耐三, 邱宁婴. 抗心律失常新药关附甲素血浓度测定的方法学研究[J]. .

Li-Li Yang, Xiang-Jing Yang, Jing-Han Liu, Nai-San Li, Ning-Ying Qiu. Studies on the Analytical Method for a New Antiarrhythmic Guanfu Base A in Rabbit Plasma[J]. .

[1]	马雷, 殷莉莉, 孙进, 何仲贵^*. 灵敏专属的HPLC法测定比格犬中非索非那定的浓度[J]. , 2005, 14(4): 246-249.
[2]	王会娟, 李馨儒, 黄燕清, 刘艳^*. 反相高效液相色谱法测定狗血浆中番茄红素的浓度[J]. , 2004, 13(4): 259-261.